Inside Health

First Stem Cell Drug Fails 2 Late-Stage Clinical Trials

By ANDREW POLLACK

Published: September 9, 2009

What might become the first drug derived from human stem cells failed in two late-stage clinical trials, dealing a setback to the drug's developer and to the stem cell field.

The developer, Osiris Therapeutics, said Tuesday that its drug, Prochymal, was no more effective, over all, than a placebo in treating a life-threatening complication of bone marrow transplantation, though certain patients seemed to be helped.

Shares of Osiris, which is based in Columbia, Md., fell 34 percent, to $8.03.

Prochymal is a preparation of mesenchymal stem cells, which are obtained from the bone marrow of healthy young adults.

Because the cells are derived from adults, they sidestep the ethical issues stemming from the destruction of human embryos needed to make embryonic stem cells. Unlike most other types of adult stem cells, mesenchymal cells grow well in culture, so thousands of doses can be produced from a single donation.

Stem cells, particularly in the form of bone marrow transplants, are already used in medicine. Osiris is hoping that Prochymal will become the first stem cell product approved by the Food and Drug Administration and sold as a mass-produced pharmaceutical product.

But the failure in the two trials could make it hard to reach that goal. Both trials tested Prochymal as a treatment for graft-versus-host disease, which occurs when immune cells in donated marrow attack the recipient's organs as foreign tissue.

In one trial, in which Prochymal was used along with steroids, 45 percent of patients responded to Prochymal and steroids compared with 46 percent who had a response to steroid and a placebo.

In a second trial, in which Prochymal was tested in patients who were not benefiting from steroids, 35 percent of those getting the drug had a resolution of graft-versus-host disease for at least 28 days, compared with 30 percent getting the placebo. The difference was not statistically significant.

Osiris said, however, that in the second trial, the drug did provide a statistically meaningful benefit in patients having graft-versus-host disease that specifically affected their livers or their gastrointestinal tracts.

C. Randal Mills, the company's chief executive, said he hoped the drug could be approved for those patients, given the seriousness of the disease. ''Prochymal is having a clear effect in the liver, and that is the most underserved patient population,'' he said in an interview.

But the F.D.A. is usually reluctant to approve a drug based on its working in only a subset of patients.

In March, Osiris stopped enrollment in a trial testing Prochymal as a treatment for Crohn's disease, saying it was unlikely the drug would be better than a placebo, because of a high positive response to the placebo. Genzyme has the right to sell Prochymal outside the United States and Canada.

Dr. Darwin J. Prockop, an expert on mesenchymal stem cells who was not involved in the trials, said there were still a lot of unknowns about how the cells work. ''Understanding it well enough to translate to the clinic -- that's the hurdle we're at,'' said Dr. Prockop, who is director of the Institute for Regenerative Medicine at Texas A&M Health Science Center.